Bis Urea Research Articles

A study on MAPK/ERK and CDK2-Cyclin-E signal switch “on and off” in cell proliferation by bis urea derivatives of 1, 4-Diisocyanatobenzene

A series of novel substituted bisurea 1,4-Diisocyanatobenzene compounds were designed, synthesized and introduced as potent anticancer compounds and screened for their in vitro anti-proliferative activities in human cancer cell lines. The structures of all titled compounds were characterized using Fourier-transform infrared mass spectra, nuclear magnetic resonance spectroscopy, elemental analysis and evaluated their sustainability using biological experiments. A selected group of ten derivatives were apprised for their anti-proliferative activity. The compounds 3d and 3e displayed potent anticancer activity with low IC50 value of 5.40, and 5.89 μM against HeLa cancer cell lines. The observed apoptosis data has demonstrated that compounds 3d and 3e induce the activaties of caspase-9 and caspase-3, the compounds 3d and 3e regulated fungal zone inhibition. Due to promising growth inhibitions, the all synthesized compounds were allowed to campaign includes quantum-polarized-ligand, quantum mechanical and molecular mechanical, docking experiments. The compounds 3d and 3e have exhibited a higher affinity for ERK/MAP kinase and CDK2 proteins. The molecular docking interactions have demonstrated two stage inhibition of cancer cells by binding with ERK/MAP kinase and CDK2 leads to inactivation of cell proliferation,cell cycle progression,cell divisionanddifferentiation, and hypo-phosphorylation of ribosome leading cells to restricts at point boundary of the G1/S phase. The long-range molecular dynamics, 150 ns, simulations were also revealed more consistency by 3d. Our study conclude good binding propensity for active-tunnel of ERK/MAP kinase and CDK2 proteins, by 3d (1,1′-(1,4-phenylene) bis(3-(2-chlorobenzyl)urea)), to suggest that the designed and synthesized 3d is to use as selective novel nuclei in anti-cancer chemotherapeutics.

Development of Poor Cell Adhesive Immersion Precipitation Membranes Based on Supramolecular Bis-Urea Polymers.

A variety of biomedical applications requires tailored membranes; fabrication through a mix-and-match approach is simple and desired. Polymers based on supramolecular bis-urea (BU) moieties are capable of modular integration through directed non-covalent stacking. Here, it is proposed that non-cell adhesive properties can be introduced in polycaprolactone-BU-based membranes by the addition of poly(ethylene glycol) (PEG)-BU during immersion precipitation membrane fabrication, while unmodified PEG is not retained in the membrane. PEG-BU addition results in denser membranes with a similar pore size compared to pristine membranes, while PEG addition induces defect formation. Infrared spectroscopy and surface hydrophobicity measurements indicate that PEG-BU is retained during membrane processing. Additionally, PEG-BU incorporation successfully leads to poor cell adhesive surfaces. No evidence is observed to indicate PEG retention. The results obtained indicate that the BU system enables intimate mixing of BU-modified polymers after processing. Collectively, the results provide the first steps toward BU-based immersion precipitated supramolecular membranes for biomedical applications.

Bisurea and Bisthiourea H-Bonding Organocatalysts for Ring-Opening Polymerization: Cues for the Catalyst Design

A series of conformationally flexible bis(thio)urea H-bond donors plus base cocatalyst were applied to the ring-opening polymerization (ROP) of lactones. The rate of the ROP displays a strong depen...

Functional peptide presentation on different hydrogen bonding biomaterials using supramolecular additives

Supramolecular biomaterials based on hydrogen bonding units can be conveniently functionalized in a mix-and-match approach using supramolecular additives. The presentation of bioactive additives has been sparsely investigated in supramolecular-based elastomeric biomaterials. Here it was investigated how cell adhesive peptides are presented and affect the surface in supramolecular biomaterials based either on ureido-pyrimidinone (UPy) or bisurea (BU) moieties. Polycaprolactone modified with UPy or BU moieties served as the base material. RGD or cyclic (c)RGD were conjugated to complementary supramolecular motifs, and were mixed with the corresponding base materials as supramolecular additives. Biomaterial surface morphology changed upon bioactivation, resulting in the formation of random aggregates on UPy-based materials, and fibrous aggregates on BU-materials. Moreover, peptide type affected aggregation morphology, in which RGD led to larger cluster formation than cRGD. Increased cRGD concentrations led to reduced focal adhesion size and cell migration velocity, and increased focal adhesion numbers in both systems, yet most prominent on functionalized BU-biomaterials. In conclusion, both systems exhibited distinct peptide presenting properties, of which the BU-system most strongly affected cellular adhesive behavior on the biomaterial. This research provided deeper insights in the differences between supramolecular elastomeric platforms, and the level of peptide introduction for biomaterial applications.

The degradation and performance of electrospun supramolecular vascular scaffolds examined upon in vitro enzymatic exposure

To maintain functionality during in situ vascular regeneration, the rate of implant degradation should be closely balanced by neo-tissue formation. It is unknown, however, how the implant’s functionality is affected by the degradation of the polymers it is composed of. We therefore examined the macro- and microscopic features as well as the mechanical performance of vascular scaffolds upon in vitro enzymatic degradation. Three candidate biomaterials with supramolecularly interacting bis-urea (BU) hard blocks (‘slow-degrading’ polycarbonate-BU (PC-BU), ‘intermediate-degrading’ polycarbonate-ester-BU (PC(e)-BU), and ‘fast-degrading’ polycaprolactone-ester-BU (PCL-BU)) were synthesized and electrospun into microporous scaffolds. These materials possess a sequence-controlled macromolecular structure, so their susceptibility to degradation is tunable by controlling the nature of the polymer backbone. The scaffolds were incubated in lipase and monitored for changes in physical, chemical, and mechanical properties. Remarkably, comparing PC-BU to PC(e)-BU, we observed that small changes in macromolecular structure led to significant differences in degradation kinetics. All three scaffold types degraded via surface erosion, which was accompanied by fiber swelling for PC-BU scaffolds, and some bulk degradation and a collapsing network for PCL-BU scaffolds. For the PC-BU and PC(e)-BU scaffolds this resulted in retention of mechanical properties, whereas for the PCL-BU scaffolds this resulted in stiffening. Our in vitro study demonstrates that vascular scaffolds, electrospun from sequence-controlled supramolecular materials with varying ester contents, not only display different susceptibilities to degradation, but also degrade via different mechanisms. Statement of SignificanceOne of the key elements to successfully engineer vascular tissues in situ, is to balance the rate of implant degradation and neo-tissue formation. Due to their tunable properties, supramolecular polymers can be customized into attractive biomaterials for vascular tissue engineering. Here, we have exploited this tunability and prepared a set of polymers with different susceptibility to degradation. The polymers, which were electrospun into microporous scaffolds, displayed not only different susceptibilities to degradation, but also obeyed different degradation mechanisms. This study illustrates how the class of supramolecular polymers continues to represent a promising group of materials for tissue engineering approaches.

The Degradation and Performance of Electrospun Supramolecular Vascular Scaffolds Examined Upon <i>In Vitro</i> Enzymatic Exposure

To maintain functionality during in situ regeneration of load-bearing tissues, a balance between the rates of implant degradation and neo-tissue formation is required. Strictly segmented thermoplastic elastomers with supramolecularly interacting bis-urea (BU) hard blocks are attractive biomaterials for vascular tissue engineering, as these polymers are soft, tough, and biodegradable. Moreover, these materials possess a sequence-controlled macromolecular structure, so their susceptibility to degradation is tunable by controlling the nature of the polymer backbone. It is unknown, however, how the implant’s functionality is affected by the degradation of the polymers it is composed of. We therefore examined the macro- and microscopic features as well as the mechanical performance of vascular scaffolds upon in vitro enzymatic degradation. Three candidate biomaterials (‘slow-degrading’ polycarbonate-BU (PC-BU), ‘intermediate-degrading’ polycarbonate-ester-BU (PC(e)-BU), and ‘fast-degrading’ polycaprolactone-ester-BU (PCL-BU)) were synthesized and electrospun into microporous scaffolds. The scaffolds were incubated in lipase and monitored for changes in physical, chemical, and mechanical properties. Remarkably, comparing PC-BU to PC(e)-BU, we observed that small changes in macromolecular structure led to significant differences in degradation kinetics. All three scaffold types degraded via surface erosion, which was accompanied by fiber swelling for PC-BU scaffolds, and some bulk degradation and a collapsing network for PCL-BU scaffolds. For the PC-BU and PC(e)-BU scaffolds this resulted in retention of mechanical properties, whereas for the PCL-BU scaffolds this resulted in stiffening. Our in vitro study demonstrates that vascular scaffolds, electrospun from sequence-controlled supramolecular materials with varying ester contents, not only display different susceptibilities to degradation, but also degrade via different mechanisms.

Dual Electrospun Supramolecular Polymer Systems for Selective Cell Migration.

Dual electrospinning can be used to make multifunctional scaffolds for regenerative medicine applications. Here, two supramolecular polymers with different material properties are electrospun simultaneously to create a multifibrous mesh. Bisurea (BU)-based polycaprolactone, an elastomer providing strength to the mesh, and ureido-pyrimidinone (UPy) modified poly(ethylene glycol) (PEG), a hydrogelator, introducing the capacity to deliver compounds upon swelling. The dual spun scaffolds are modularly tuned by mixing UPyPEG hydrogelators with different polymer lengths, to control swelling of the hydrogel fiber, while maintaining the mechanical properties of the scaffold. Stromal cell derived factor 1 alpha (SDF1α) peptides are embedded in the UPyPEG fibers. The swelling and erosion of UPyPEG increase void spaces and released the SDF1α peptide. The functionalized scaffolds demonstrate preferential lymphocyte recruitment proposed to be created by a gradient formed by the released SDF1α peptide. This delivery approach offers the potential to develop multifibrous scaffolds with various functions.

Studies on organogelation of self assembling bis urea type low molecular weight molecules

A novel class of toluene based bis urea compounds carrying linear fatty acid units and semicarbazide linkages has been synthesised. The compounds were exhibiting thermoreversible gelation at concentrations below 10 mg/mL in common organic solvents, both aliphatic and aromatic. The effect of the chain length variation of fatty acid units on gelation properties like gelation concentration, gelation time and gel melting temperatures were studied. Choosing a particular gelator of fixed chain length and a specific solvent, the effect of the concentration on the gelation properties were studied. The thermal studies using DSC revealed the presence of phase transitions corresponding to the premelting and melting of the gels during the heating cycle. The morphology of the xerogels studied using SEM revealed a three dimensional network structure while the WAXS studies showed no crystallinity in the xerogels. IR spectra of the gels (solvent subtracted) and solutions in the corresponding solvent showed that a high degree of inter-molecular H bonding exists and absorptions corresponding to NH stretching shifted to lower wave numbers. Thus simple bisurea type of compounds exhibiting gelation ability in a wide range of solvents can be used for making functional gels for various applications.

Synthesis of organic bisurea compounds and their roles as crystallization nucleating agents of poly(l-lactic acid)

A series of novel organic bisurea (BUr) compounds were facilely synthesized from phenyl isocyanate and a variety of diamines, and their roles as crystallization nucleating agents of commercial poly(l-lactic acid) (PLLA) were investigated through differential scanning calorimetry (DSC), polarized optical microscopy (POM) and wide-angle X-ray diffraction (WAXD). Their crystallization accelerating efficiency depends on the methylene numbers in molecular structure: the less the CH2 number, the faster the crystallization rate. Among them, 1,1′-(ethane-1,2-diyl)bis(3-phenylurea) (BUr1) acts as the most effective crystallization accelerating agent. In the presence of ca. 2wt% BUr1, the melt crystallization enthalpy of PLLA increases from almost 0 to 31.2J/g under cooling rate of 10°C/min, and the isothermal melt crystallization rate (t1/2-1) increased by 10.5 times at 140°C. Much higher nucleation density and smaller spherulite size of PLLA were observed by POM, indicating obvious heterogeneous nucleation effect. And the crystal structure of PLLA remains unchanged after incorporation of the nucleator.

Recognition of Anions by bis Urea based Fluorescent Receptors

Three bis urea based acyclic receptors with fixed spacer and varying size of substituents have been synthesized and their binding behavior with different anions are reported along with the selectivity of these receptors towards anions. The fluorescence quenching of the receptors 2 and 3 on binding with anions is also shown. The receptor 1 binds better with Y-shaped AcO¯ ion whereas receptor 3 binds well with Cl¯ ion. Keywords: Anion recognition, fluorescence sensing, urea, acyclic receptors

Hydrogen bonding in oxalic acid and its complexes: A database study of neutron structures

The basic result of carboxylic group that the oxygen atom of the -OH never seems to be a hydrogen bond acceptor is violated in the cases, namely urea oxalic acid and bis urea oxalic acid complexes, where the hydroxyl oxygen atom is an acceptor of a weak N—H… O hydrogen bond. The parameters of this hydrogen bond, respectively in these structures are: hydrogen acceptor distance 2.110 A and 2.127 A and the bending angle at hydrogen, 165.6° and 165.8°. The bond strength around the hydroxyl oxygen is close to 1.91 valence units, indicating that it has hardly any strength left to form hydrogen bonds. These two structures being highly planar, force the formation of this hydrogen bond. As oxalic acid is the common moiety, the structures of the two polymorphs, α-oxalic acid and β-oxalic acid, also were looked into in terms of hydrogen bonding and packing.